Claims
- 1. A process for preparing a substantially optically pure psorospermin or analog of the formula:
- 2. The process of claim 1, wherein deprotecting conditions in the deprotection step comprise Pd/BaSO4 and 1,4-cyclohexadiene, or Raney Nickel.
- 3. The process of claim 1, wherein R2 is OH after the deprotecting step
wherein the process further comprises alkylating 57wherein R2 is OR2′ where R2′ is alkyl after the alkylating step.
- 4. The process of claim 1 further comprising before the hydrogenating step, chirally epoxidizing
- 5. The process of claim 4 wherein either of
- 6. The process of claim 4 further comprising before the chiral epoxidizing step, forming an unsaturated ester under either cis- or trans-directing reaction conditions
- 7. The process of claim 6, wherein the cis ester is separated from the trans ester.
- 8. The process of claim 7, wherein the cis ester is separated by recrystalization from ethylacetate.
- 9. The process of claim 6 wherein the cis-directing reaction conditions are (CF3CH2O)2POCH(R3)CO2Me or (PhO)2POCH(R3)CO2R, where R is an alkyl group and Ph can be substituted, in KHMDS/18-crown-6 and the trans-directing reaction conditions (CH3CH2O)2POCH(R3)CO2R wherein R is alkyl; and wherein the ester is reduced with DIBALH.
- 10. The process of claim 6 further comprising before the esterifying step, selectively protecting the hydroxyl group at the 3 position and a hydroxyl group at the 5 position, if R2 is OH as in the following compound:
- 11. The process of claim 10, wherein the protecting group on the hydroxyl group at the 3 and 5 positions is a benzyl group.
- 12. The process of claim 10, further comprising before the protecting step, dealkylating
- 13. The process of claim 12, wherein R1 and R2 are each methyl before the dealkylating step and BBr3 is used as a demethylation agent in the dealkylating step.
- 14. The process of claim 12 further comprising before the dealkylating step rearranging
- 15. The process of claim 14 wherein the Claisen conditions comprise heating about 190° C.
- 16 The process of claim 1, wherein R,R psorospermin is produced.
- 17. The process of claim 1, wherein R,S psorospermin is produced.
- 18. The process of claim 1, wherein S,R psorospermin is produced.
- 19. The process of claim 1, wherein S,S psorospermin is produced.
- 20. The process of claim 1, wherein R,R 5-methoxypsorospermin is produced.
- 21. The process of claim 1, wherein R,S 5-methoxypsorospermin is produced.
- 22. The process of claim 1, wherein S,R 5-methoxypsorospermin is produced.
- 23. The process of claim 1, wherein S,S 5-methoxypsorospermin is produced.
- 24. A method inhibiting cell proliferation comprising contacting a cell with an effective amount of a compound produced by the process of claim 1.
- 25. A pharmaceutical composition comprising the substantially optically pure compound produced by the process in claim 1, and a pharmaceutically acceptable carrier.
RELATED APPLICATIONS
[0001] This application is related to U.S. provisional application No. 60/407,347 filed Aug. 30, 2002. The content of this application is incorporated herein by reference in its entirety.
Provisional Applications (1)
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Number |
Date |
Country |
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60407347 |
Aug 2002 |
US |